Inclusion Criteria

Inclusion Criteria

- Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma
of the colon or rectum with measurable disease (patients who have become resistant or
intolerant of at least one-line of chemotherapy regimen are eligible)

- Patients who had had previous treatment with Irinotecan and who have definite
progression on Irinotecan are eligible provided they are not a candidate for other
therapeutic treatment options. Definitive progression is defined as progression of
disease while on Irinotecan or within 4 weeks of discontinuing Irinotecan.

- ≥ 18 years old

- ECOG performance status ≤ 2 (Karnofsky > 60%)

- ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL

- Serum bilirubin within normal range (or < 1.5 x IULN if liver metastases present; or
total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients
with well documented Gilbert Syndrome)

- AST (SGOT) or ALT (SGPT) within normal range (or ≤ 3.0 x upper limit of normal if
liver metastases present)

- adequate renal function as evidenced by creatinine ≤ 1.5 x IULN or creatinine
clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional
normal.

- serum calcium (corrected for serum albumin) within normal limits. Biphosphonate use
for malignant hypercalcemia control is not allowed.

- Serum magnesium ≥ the institutional lower limit of normal (ILLN) and potassium within
institutional normal limits.

- serum lipase ≤ IULN; serum amylase ≤ IULN; fasting plasma glucose ≤ 120 mg/dL (6.7
mmol/L)

- females of child-bearing potential must have negative serum pregnancy test within 72
hours prior to treatment. Cannot be pregnant or nursing.

- Males and females must agree to use effective contraceptive method.

- INR ≤ 2 Exclusion Criteria

- Previous treatment with chemotherapy, biologic therapy, or wide field radiotherapy <
4 weeks or limited field radiation for palliation < 2 weeks prior to starting study
drug; must have recovered from side effects of such therapy

- Known hypersensitivity to BKM120 or to its excipients or to irinotecan

- Untreated brain metastases. Patients with metastatic CNS tumors may participate in
this trial, if the patient is > 4 weeks from therapy completion, is clinically stable
and is not receiving corticosteroid therapy

- Known polymorphism in UGTAIA or Gilbert's syndrome

- Acute or chronic liver, renal disease or pancreatitis

- Medically documented history or active major depressive episode, bipolar disorder (I
or II), obsessive-compulsive disorder, schizophrenia, history of suicidal attempt or
ideation, or homicidal ideation; ≥ CTCAE grade 3 anxiety; meets cutoff score of ≥ 10
in the PHQ-9 or cut-off of ≥ 15 in GAD-7 mood scale, respectively, or selects
positive response of "1, 2, or 3" to question number 9 regarding potential for
suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)

- Clinically significant heart disease including: Left ventricular ejection fraction
(LVEF) <50% as determined by echocardiogram; ventricular arrhythmias except for
benign premature ventricular contractions; supraventricular and nodal arrhythmias
requiring a pacemaker or not controlled with medication; conduction abnormality
requiring a pacemaker; valvular disease with documented compromised cardiac function;
symptomatic pericarditis; QTc > 480 msec on screening ECG (using QTcF formula; angina
pectoris that requires use of anti-anginal medication

- History of cardiac dysfunction including: acute myocardial infarction ≤ 6 months,
documented by persistent elevated cardiac enzymes or persistent regional wall
abnormalities on assessment of LVEF function; history of documented congestive heart
failure (NYHA Class III or IV; document cardiomyopathy

- Other concurrent severe and/or uncontrolled concomitant medical conditions

- Significant symptomatic deterioration of lung function. If clinically indicated,
pulmonary function tests including measures of predicted lung volumes, DLco, O2
saturation at rest on room air should be considered to exclude pneumonitis or
pulmonary infiltrates

- Clinical manifestation of diabetes mellitus or steroid-induced diabetes mellitus

- Impairment of GI function or disease that may significantly alter the absorption of
BKM120; diarrhea ≥ grade 2

- Major surgery ≤ 4 weeks prior to starting study drug

- Prior treatment with a P13K inhibitor; any hematopoietic colony-stimulating growth
factors ≤ 2 weeks prior to starting study drug; corticosteroids ≤ 2 weeks prior to
starting study drug; chemotherapy or targeted anticancer therapy ≤4 weeks (6 weeks
for nitrosourea, antibodies or mitomycin-C) prior to starting study drug; small
molecule therapeutics (excluding monoclonal antibodies) ≤5 effective half-lives prior
to starting study drug

- Currently receiving medication that has the potential to prolong the QT interval or
inducing Torsades de Pointes

- chronic treatment with steroids or another immunosuppressive agent. Note: Topical
applications (eg rash), inhaled sprays (eg obstructive airways diseases), eye drops
or local injections (eg intra-articular) are allowed. Patients with previously
treated brain metastases, who are on stable low dose corticosteroids treatment (eg
dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of
study treatment are eligible.

- therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.

- any medications or substances that are inhibitors or inducers of specific CYP450
enzyme(s).

- any other study agents

- Patients who have taken herbal medications and certain fruits within 7 days prior to
starting study drug. Herbal medications include, but are not limited to St. John's
wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA),
yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville
oranges, grapefruit, pummelos, or exotic citrus fruits.

- Patients who have received wide field radiotherapy ≤ 4 weeks or limited field
radiation for palliation ≤ 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy

- Women who are pregnant or breast feeding; adults of reproductive potential not using
an effective method of birth control.

- Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (eg age appropriate, history of vasomotor symptoms) or 6 months of
spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or
have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6
weeks ago. In the case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment is she considered
not of child bearing potential.

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, must use highly effective contraception during treatment for 8
days after stopping treatment and for additional 12 weeks after study drug
discontinuation. Highly effective contraception is defined as: true abstinence:
Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not acceptable methods of contraception. Sterilization: have had
surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at
least 6 weeks ago. In case of oophorectomy alone, only when the reproductive status
of the woman has been confirmed by follow up hormone level assessment.

- Male partner sterilization (with the appropriate post-vasectomy documentation of the
absence of sperm in the ejaculate). For female subjects on the study, the
vasectomised male partner should be the sole partner for that patient.

- Use of a combination of any two of the following (a+b): Placement of an intrauterine
device (IUD) or intrauterine system (IUS); Barrier methods of contraception: Condom
or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository; Oral contraception, injected or implanted
hormonal methods are not allowed as BKM120 potentially decreases the effectiveness of
hormonal contraceptives.

- Fertile males must use condom during treatment, for 8 days after stopping treatment
and for additional 12 weeks after study drug discontinuation and should not father a
child in this period.

- Known diagnosis of human immunodeficiency virus (HIV) infection

- History of another malignancy within 3 years, except cured basal cell skin carcinoma
or excised cervical carcinoma in situ

- Previous treatment with Irinotecan who have definite progression on Irinotecan.